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Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus.Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease.What is Known:• Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI• AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68.What is New:• Improving knowledge on AFM must increase early recognition and adequate diagnostic procedures by clinicians.• The increasing incidence of AFM urges cooperation between pediatricians, neurologists, and microbiologists for the development of treatment and preventive options.

ObjectiveTo report the clinical and immunological characteristics of 22 new patients with glial fibrillar acidic protein (GFAP) autoantibodies.MethodsFrom January 2012 to March 2017, we recruited 451 patients with suspected neurological autoimmune disease at the Catholic University of Rome. Patients’ serum and cerebrospinal fluid (CSF) samples were tested for neural autoantibodies by immunohistochemistry on mouse and rat brain sections, by cell-based assays (CBA) and immunoblot. GFAP autoantibodies were detected by immunohistochemistry and their specificity confirmed by CBA using cells expressing human GFAPα and GFAPδ proteins, by immunoblot and immunohistochemistry on GFAP-/- mouse brain sections.ResultsSerum and/or CSF IgG of 22/451 (5%) patients bound to human GFAP, of which 22/22 bound to GFAPα, 14/22 to both GFAPα and GFAPδ and none to the GFAPδ isoform only. The neurological presentation was: meningoencephalomyelitis or encephalitis in 10, movement disorder (choreoathetosis or myoclonus) in 3, anti-epileptic drugs (AED)-resistant epilepsy in 3, cerebellar ataxia in 3, myelitis in 2, optic neuritis in 1 patient. Coexisting neural autoantibodies were detected in five patients. Six patients had other autoimmune diseases. Tumours were found in 3/22 patients (breast carcinoma, 1; ovarian carcinoma, 1; thymoma, 1). Nineteen patients were treated with immunotherapy and 16 patients (84%) improved. Histopathology analysis of the leptomeningeal biopsy specimen from one patient revealed a mononuclear infiltrate with macrophages and CD8+ T cells.ConclusionsGFAP autoimmunity is not rare. The clinical spectrum encompasses meningoencephalitis, myelitis, movement disorders, epilepsy and cerebellar ataxia. Coexisting neurological and systemic autoimmunity are relatively common. Immunotherapy is beneficial in most cases.

A mouse model of enterovirus D68 (EV-D68) paralytic myelitis can be used to evaluate the efficacy of possible treatment options for EV-D68–associated central nervous system disease. Abstract Background Enterovirus D68 (EV-D68)–associated acute flaccid myelitis (AFM) is a devastating neurological disease for which there are no treatments of proven efficacy. The unpredictable temporal and geographic distribution of cases and the rarity of the disease make it unlikely that data from randomized controlled trials will be available to guide therapeutic decisions. We evaluated the following 3 widely used empirical therapies for the ability to reduce the severity of paralysis in a mouse model of EV-D68 infection: (1) human intravenous immunoglobulin (hIVIG), (2) fluoxetine, and (3) dexamethasone. Methods Neonatal mice were injected intramuscularly with a human 2014 EV-D68 isolate that reliably induces paralysis in mice due to infection and loss of spinal cord motor neurons. Mice receiving treatments were evaluated for motor impairment, mortality, and spinal cord viral load. Results hIVIG, which contained neutralizing antibodies to EV-D68, reduced paralysis in infected mice and decreased spinal cord viral loads. Fluoxetine had no effect on motor impairment or viral loads. Dexamethasone treatment worsened motor impairment, increased mortality, and increased viral loads. Conclusion Results in this model of EV-D68–associated AFM provide a rational basis for selecting empirical therapy in humans and establish this model as a useful system for evaluating other potential therapies.

Abstract BackgroundFampridine is a potassium channel blocker drug used to improve walking ability in patients with multiple sclerosis (MS). We evaluated the effect of fampridine in patients with MS in the acute phase of transverse myelitis.MethodsIn a randomized, placebo-controlled trial, 30 patients who had their first episode of cervical myelitis with quadriparesis presentation, with the final diagnosis of MS, were randomly divided into two equal groups. The intervention group received intravenous methylprednisolone (IVMP) for 7 days plus fampridine. The placebo group received IVMP for 7 days plus placebo. To compare the treatment results, we compared the Barthel index (BI) scores of the groups at the start of the trial and the 21st day after the start of treatment.ResultsThere was no significant difference in baseline characteristics between the intervention and placebo groups in terms of mean age, sex, and mean admission BI (p > 0.05). Mean (SD) admission BI in placebo and intervention groups was 27.20 (7.341) and 27.87(5.78), respectively (p = 0.784). The measured mean (SD) BI after treatment was 48.73 (15.54) in the placebo and 64.93 (11.81) in the intervention group (p = 0.003) after 3 weeks.ConclusionUsing fampridine plus IVMP in the acute phase of transverse myelitis in MS patients improved the disease’s symptoms and increased the daily activity ability of patients.

Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence.

Neurological sequelae of coronavirus disease 2019 (COVID-19) include inflammatory myelopathies. Among these, magnetic resonance imaging (MRI)-negative myelitis- defined as normal spinal cord MRI findings despite compatible clinical features-presents diagnostic and therapeutic challenges. A 22-year-old Japanese woman developed progressive distal paresthesia, gait disturbance, bladder and rectal dysfunction, and sensory loss approximately three months after COVID-19. Neurological examination presented with pyramidal tract signs and sensory deficits in both lower limbs. Cerebrospinal fluid oligoclonal bands were positive. Brain MRI showed subtle corticospinal tract hyperintensities, whereas spinal MRI findings remained normal throughout the course. Somatosensory-evoked potentials (SEP) demonstrated absent right N20 and bilateral P37 responses, localizing dysfunction to the thoracic cord. Treatment with intravenous methylprednisolone pulse therapy with plasma exchange resulted in marked clinical recovery and SEP normalization, with only mild residual paresthesia at two-year follow-up. The present case illustrates the clinical utility of SEPs for monitoring disease activity and establishing objective criteria for treatment escalation in post-COVID-19 MRI-negative myelitis. Although MRI-negative myelitis can be observed in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lupus myelitis, and glial fibrillary acidic protein (GFAP) astrocytopathy, post-COVID-19 myelitis lacks specific biomarkers, complicating both diagnosis and treatment. A review of 20 reported cases of post-COVID-19 MRI-negative myelitis revealed a mean age of 54.4 years, a male-to-female ratio of 3:2, frequent bladder and rectal disturbances and paresis (85% each), high severity (63.2%), a median infection-to-neurological interval of 28 days, oligoclonal bands in 25% (4/16), multiple immunotherapies in 66.7%, and marked improvement or recovery in 66.7%. In post-COVID-19 MRI-negative myelitis, SEPs offer critical diagnostic and prognostic information. Early recognition and timely escalation of combination immunotherapy may optimize neurological outcomes.

BackgroundIncomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immunoadsorption are widely used in neuroimmunology. Data on apheresis outcomes in MOGAD attacks remain limited.MethodsWe retrospectively evaluated all apheresis treated attacks occurring in patients with MOGAD between 2008 and 2023 at 18 Neuromyelitis Optica Study Group centres. Treatment response was categorised as complete, partial or no remission. Preattack and follow-up Expanded Disability Status Scale (EDSS) and visual Functional System Scores (FSS) were used to calculate absolute outcomes (ΔEDSS/Δvisual FSS). Predictors of complete remission were analysed using a generalised linear mixed model.ResultsApheresis was used for 117/571 (20.5%) attacks in 85/209 (40.7%) patients. Attacks with simultaneous optic neuritis and myelitis were treated more often with apheresis (42.4%, n=14) than isolated myelitis (25.2%, n=35), cerebral manifestation (21.0%, n=17) or isolated optic neuritis (17.6%, n=51). Apheresis was initiated as first-line therapy in 12% (4.5 (IQR 0–11) days after attack onset), second-line therapy in 62% (15 (IQR 6.75–31) days) and third-line therapy in 26% (30 (IQR 19–42) days). Complete remission was achieved in 21%, partial remission in 70% and no remission in 9% of patients. First-line apheresis (OR 2.5, p=0.040) and concomitant disease-modifying therapy (OR 1.5, p=0.011) were associated with complete remission. Both parameters were also associated with a favourable ΔEDSS. No differences in outcomes were observed between the apheresis types.ConclusionApheresis is frequently used in MOGAD attacks. An early start as first-line therapy and concomitant disease-modifying therapy predict full attack recovery.

ObjectiveWe characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.MethodsWe evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.ResultsThe most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).ConclusionRelapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.

[...]the patient developed paraplegia, became wheelchair-bound, and developed weakness in her hands. Follow-up brain and cervical spine MRI with and without contrast 8 months after her last MRI showed significant improvement of the T2/FLAIR signal abnormality that had been seen involving the corticospinal tracts within the corona radiata extending to the posterior limb of the internal capsules bilaterally, without restricted diffusion or enhancement (Fig. 1 A). The SARS-CoV genome has been detected in the cytoplasm of neurons in the brain; thus, it is likely that SARS-CoV-2, given its similar invasion mechanism, can lead to neuronal dysfunction either directly or indirectly through immune-mediated mechanisms [2].

Objective This study aims to investigate the relationship between treatment delay and poor prognosis in acute myelitis of Neuromyelitis Optica Spectrum Disorder (NMOSD). Additionally, we seek to explore the related factors that contribute to poor prognosis, with the intention of providing more precise clinical guidance. Methods We retrospectively analyzed the acute myelitis attacks of NMOSD patients who were continuously followed up or referred to our hospital from January 2018 to September 2022. We further calculated the proportion of clinical score improvement: (acute‐follow‐up)/(acute‐baseline); poor prognosis was assigned to 0%–33% improvement. The relationship between treatment delay and poor prognosis was evaluated with clustered Receiver Operating Characteristic (ROC) analysis. A Generalized linear mixed model was used to analyze the related factors. Results This study included a total of 144 episodes of myelitis attacks, of which 21.5% (31/144) resulted in poor prognosis. Based on the results of the clustered ROC analysis, it has been determined that treatment delay holds significant predictive value for poor prognosis (p = 0.001), with the optimal cut‐off point being 15 days. The generalized linear mixed model revealed that factors contributing to poor prognosis in NMOSD myelitis include age (OR, 1.041; CI, 1.013–1.071; p = 0.004) and treatment delay (OR, 1.034; CI, 1.014–1.054; p = 0.001). Conclusion Our results confirm the treatment delay and age as predictors of poor prognosis in acute myelitis of NMOSD. This study aims to explore the related factors that contribute to poor prognosis in acute myelitis of neuromyelitis optica spectrum disorder. Our results confirm the treatment delay and age at attack as predictors of poor prognosis.